Cutaneous Lymphomas

ICD-11

2B33.5

Synonyms

Cutaneous T-cell lymphomas (CTCL), cutaneous B-cell lymphomas (CBCL).

Epidemiology

Rare diseases (1/100 000).

Definition

Cutaneous lymphomas are a heterogeneous group of non-Hodgkin lymphomas that primarily involve the skin.

Aetiology & Pathogenesis

Unknown in most cases. Older age, viral infection in some cases (HTLV-1, EBV). Antigen persistence.

Signs & Symptoms

Symptoms of primary cutaneous lymphomas vary depending on the subtype.

Erythematous, hypopigmented or poikilodermic macules or patches with mild scaling can be found in mycosis fungoides (the most frequent CTCL). In advanced stages nodules develop. Pruritus is frequent. Erythroderma is characteristic for Sézary syndrome. B-cell lymphomas characteristically appear with dome-shaped red papules and nodules, which may become large aggregates.

Localisation

Cutaneous lymphomas can appear anywhere on the body, localisation may depend on the subtype of lymphoma. Early mycosis fungoides is located on sun-protected areas.

Classification

Primary cutaneous lymphomas are classified by the WHO-EORTC classification system. CTCL account for approximately 75% of the cases, of which mycosis fungoides is the most frequent one. The remaining 25% are CBCL.

Laboratory & other workups

Serologic testing for lymphotropic viruses (HIV, EBV, HTLV-1), LDH, flow cytometry (CD3, CD4, CD8, loss of CD26 and CD7), T or B-cell clonality in skin +/- blood by PCR tests or high throughput sequencing. Staging should be according to the TNMB (Tumor nodes metastasis blood) classification.

Dermatopathology

Cutaneous lymphomas are a proliferation of lymphocytes with variable size, atypia, architecture, and immunophenotype, depending on the subtype.

CTCL: infiltrate of small to medium mononuclear cells with mild to moderate atypia in the upper dermis with epidermotropism (T-cell pattern). Immunohistochemistry is used to describe the cell of origin (e.g., anti-CD3 for T cells, CD20 for B cells) and the histological subtype.

Course

Prognosis of primary cutaneous lymphomas depends on the subtype and stage and is generally considered better than primary nodal lymphomas. The majority of mycosis fungoides and CBCL cases have an indolent evolution.

Complications

Many cutaneous lymphomas show no or slow evolvement. Erythroderma types are accompanied with severe pruritus and often loss of protein and trace elements via desquamation. Large nodular aggregates at groin or axillary regions can stop lymph drainage. In case of advanced-stage or aggressive form, immunosuppression may lead to cutaneous and systemic infections. Lymphoma progression (nodal involvement, visceral involvement) may occur.

Diagnosis

The precise diagnosis of cutaneous lymphomas is always obtained by clinical-histological correlation.

Differential diagnosis

Differential diagnoses for patch stage mycosis fungoides: contact dermatitis, atopic dermatitis, psoriasis, parapsoriasis, pseudolymphomas. In tumour stage CTCL or CBCL: other primary or secondary lymphomas or other tumours.

Prevention & Therapy

The treatment should be adjusted to the subtype (indolent or aggressive) and stage (early or advanced).

Skin directed treatments (topical corticosteroids, phototherapy, topical chlormethine / carmustine / nitrogen mustard) in early stage mycosis fungoides. Systemic treatments (methotrexate, bexarotene, peg interferon), radiotherapy, HDAC (histone desacetylase) inhibitors, immunotherapies (photophoresis in erythrodermic subtypes, monoclonal antibodies) or chemotherapy in advanced stage.

Indolent B-cell lymphomas may be treated by surgical excision, radiation therapy, topical steroids, or rituximab (anti-CD20 antibody) in disseminated cases. Aggressive B-cell lymphomas usually require rituximab and polychemotherapy.

Special

Early aggressive treatment modalities must be avoided, unless systemic involvement has been documented (blood, lymph nodes, internal organs).

3.3.12 Cutaneous Lymphomas